Synthesis of 4-Alkynylpyrrolo[2,3-d]pyrimidines by Palladium-Catalyzed Cross-Coupling Reactions

Abstract

The palladium-catalyzed cross-coupling reaction of methyl­ 5-amino-4-chloro- and 5-amino-4-iodo-7-methyl-2-(methylsulfanyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate with various terminal alkynes has been investigated. The 4-iodo derivative was found to be a good substrate for the synthesis of various 4-alkynylpyrrolopyrimidines. A simple synthesis of 4-(indol-2-yl)pyrrolo[2,3-d]pyrimidines by the reaction of 4-iodopyrrolopyrimidine with 2-ethynyl-N-mesylaniline in the presence dichlorobis(triphenylphosphine)palladium and copper(I) iodide is described.

palladium - alkyne - catalysis - heterocycle - pyrrolopyrimidine - cyclization

References

<A NAME="RT11307SS-1A">1a</A> Modern Acetylene Chemistry   Stang PJ. Diederich F. VCH; Weinheim: 1995. 

<A NAME="RT11307SS-1B">1b</A> Chemistry of Triple-Bonded Functional Groups   Patai S. Wiley; New York: 1994. 

<A NAME="RT11307SS-2">2</A> Chemistry and Biology of Naturally Occurring Acetylenes and Related Compounds   Lam J. Breteler H. Arnason T. Hansen L. Elsevier; Amsterdam: 1988. 

<A NAME="RT11307SS-3A">3a</A> Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  16:  4467 

<A NAME="RT11307SS-3B">3b</A> Sonogashira K. J. Organomet. Chem.  2002,  653:  46 

<A NAME="RT11307SS-4A">4a</A> Tsuji J. Palladium Reagents and Catalysts   Wiley; New York: 1999. 

<A NAME="RT11307SS-4B">4b</A> Li JK. Gribble GW. Palladium in Heterocyclic Chemistry   Pergamon; Oxford: 2000. 

<A NAME="RT11307SS-5A">5a</A> Townsend LB, Lewis AF, and Roti Roti LW. inventors; US  804601.  ; Chem. Abstr. 1978, 89, 44130

<A NAME="RT11307SS-5B">5b</A> Porcari AR. Ptak RG. Borysko KZ. Breitenbach JM. Vittori S. Wotring LL. Drach JC. Townsend LB. J. Med. Chem.  2000,  43:  2438 

<A NAME="RT11307SS-5C">5c</A> Gangjee A. Jain HD. Phan J. Lin X. Song X. McGuire JJ. Kisliuk RL. J. Med. Chem.  2006,  49:  1055 

<A NAME="RT11307SS-5D">5d</A> Gangjee A. Lin X. Queener SF. J. Med. Chem.  2004,  47:  3689 

<A NAME="RT11307SS-5E">5e</A> Taylor EC. Kuhnt D. Shih C. Rinzel SM. Grindey GB. Barredo J. Jannatipour M. Moran RG. J. Med. Chem.  1992,  35:  4450 

<A NAME="RT11307SS-5F">5f</A> Edstrom ED. Wei I. J. Org. Chem.  1993,  58:  403 

<A NAME="RT11307SS-6A">6a</A> Seela F. Zulauf M. Helv. Chim. Acta  1999,  82:  1878 

<A NAME="RT11307SS-6B">6b</A> Zhang L. Zhang Y. Li X. Zhang L. Bioorg. Med. Chem.  2002,  10:  907 

<A NAME="RT11307SS-6C">6c</A> Taylor EC. Jennings LD. Mao Z. Hu B. Jun J.-G. Zhou P. J. Org. Chem.  1997,  62:  5392 

<A NAME="RT11307SS-6D">6d</A> Taylor EC. Chaudhuri RP. Watson SE. Tetrahedron  1999,  55:  1631 

<A NAME="RT11307SS-6E">6e</A> Gangjee A. Yu J. McGuire JJ. Cody V. Galitsky N. Kisliuk RL. Queener SF. J. Med. Chem.  2000,  43:  3837 

<A NAME="RT11307SS-6F">6f</A> Taylor EC. Young WB. Spanka C. J. Org. Chem.  1996,  61:  1261 

<A NAME="RT11307SS-6G">6g</A> Hobbs FW. J. Org. Chem.  1989,  54:  3420 

<A NAME="RT11307SS-6H">6h</A> Seela F. Zulauf M. Synthesis  1996,  726 

<A NAME="RT11307SS-6I">6i</A> Seela F. Zulauf M. Deimel M. Helv. Chim. Acta  2000,  83:  910 

<A NAME="RT11307SS-7A">7a</A> Agrofoglio LA. Gillaizeau I. Saito Y. Chem. Rev.  2003,  103:  1875 

<A NAME="RT11307SS-7B">7b</A> Schroter S. Stock C. Bach T. Tetrahedron  2005,  61:  2245 

<A NAME="RT11307SS-8">8</A> Tumkevicius S. Masevicius V. Synlett  2004,  2327 

<A NAME="RT11307SS-9">9</A> Tumkevicius S. Sarakauskaite Z. Masevicius V. Synthesis  2003,  1377 

<A NAME="RT11307SS-10A">10a</A> Rudisill DE. Stille JK. J. Org. Chem.  1989,  54:  5856 

<A NAME="RT11307SS-10B">10b</A> Yu MS. Leon LL. McGuire MA. Botha G. Tetrahedron Lett.  1998,  39:  9347 

<A NAME="RT11307SS-10C">10c</A> Arcadi A. Cacchi S. Marinelli F. Tetrahedron Lett.  1989,  30:  2581 

<A NAME="RT11307SS-11A">11a</A> Ezquerra J. Pedregal C. Lamas C. Barluenga J. Perez M. Garcia-Martin MA. Gonzalez JM. J. Org. Chem.  1996,  61:  5804 

<A NAME="RT11307SS-11B">11b</A> Ma C. Liu X. Li X. Flippen-Anderson J. Yu S. Cook JM. J. Org. Chem.  2001,  66:  4525 

<A NAME="RT11307SS-11C">11c</A> Reboredo FJ. Treus M. Estevez JC. Castedo L. Estevez RJ. Synlett  2003,  1603 

<A NAME="RT11307SS-12A">12a</A> Yasuhara A. Kanamori Y. Kaneko M. Numata A. Kondo Y. Sakamoto T. J. Chem. Soc., Perkin Trans. 1  1999,  529 

<A NAME="RT11307SS-12B">12b</A> Cacchi S. Fabrizi G. Lamba D. Marinelli F. Parisi LM. Synthesis  2003,  728 

<A NAME="RT11307SS-13">13</A> Kunckell F. Chem. Zentralblatt  1913,  1:  1768 

<A NAME="RT11307SS-14">14</A> Pedersen DS. Rosenbohm C. Synthesis  2001,  2431 

<A NAME="RT11307SS-15">15</A> Forbes IT. Johnson CN. Thompson M. Synth. Commun.  1993,  23:  715